Synaptic Potentiation Is Critical for Rapid Antidepressant Response to Ketamine in Treatment-Resistant Major Depression

Biological Psychiatry, 04/26/2012Cornwell BR et al.

The findings suggest N–methyl–D–aspartate receptor (NMDAR) antagonism does not lead directly to increased cortical excitability hours later and thus might not be sufficient for therapeutic effects of ketamine to take hold. Rather, increased cortical excitability as depressive symptoms improve is consistent with the hypothesis that enhanced non–NMDAR–mediated glutamatergic neurotransmission via synaptic potentiation is central to the antidepressant effect of ketamine.

Methods

Magnetoencephalographic recordings were made approximately 3 days before and approximately 6.5 hours after the infusion, whereas patients passively received tactile stimulation to the right and left index fingers and also while they rested (eyes-closed).